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排序方式: 共有178条查询结果,搜索用时 15 毫秒
1.
Z Yilmaz T Renton Y Yiangou J Zakrzewska I P Chessell C Bountra P Anand 《Journal of clinical neuroscience》2007,14(9):864-871
Burning mouth syndrome (BMS) is often an idiopathic chronic and intractable pain condition, affecting 1.5-5.5% of middle-aged and elderly women. We have studied the heat and capsaicin receptor TRPV1, and its regulator nerve growth factor (NGF), in BMS. Patients with BMS (n=10) and controls (n=10) were assessed for baseline and post-topical capsaicin pain scores, and their tongue biopsies immunostained for TRPV1, NGF, and structural nerve markers neurofilament and peripherin. Nerve fibres penetrating the epithelium were less abundant in BMS (p<0.0001), indicating a small fibre neuropathy. TRPV1-positive fibres were overall significantly increased in BMS (p=0.0011), as were NGF fibres (p<0.0001) and basal epithelial cell NGF staining (p<0.0147). There was a significant correlation between the baseline pain score and TRPV1 (p=0.0143) and NGF fibres (p=0.0252). A significant correlation was observed between baseline and post-capsaicin pain (p=0.0006). Selective TRPV1 and NGF blockers may provide a new therapy for BMS. 相似文献
2.
Alex W Wilson Stephen J Medhurst Claire I Dixon Nick C Bontoft Lisa A Winyard Kim T Brackenborough Jorge De Alba Christopher J Clarke Martin J Gunthorpe Gareth A Hicks Chas Bountra Daniel S McQueen Iain P Chessell 《European Journal of Pain》2006,10(6):537-549
Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic. 相似文献
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Lalam RK Cassar-Pullicino VN Mangham DC Mangham C Clewer G Cool P 《Skeletal radiology》2006,35(11):882-881
Although the rare complication of squamous cell carcinoma in chronic osteomyelitis is well known, benign squamous epithelial proliferation can also occur, causing osteolysis and fracture. The radiological and correlated pathological features of osteolysis from this benign complication of chronic osteomyelitis are presented.An erratum to this article can be found at 相似文献
5.
Pouwer F Skinner TC Pibernik-Okanovic M Beekman AT Cradock S Szabo S Metelko Z Snoek FJ 《Diabetes research and clinical practice》2005,70(2):166-173
It has been hypothesized that coverage of diabetes-specific issues (e.g. coping with complications, incapacity, pain) during psychotherapy may optimize the likelihood of treatment success for depression in patients with diabetes. However, it is still unclear how often depression is confounded by diabetes-specific emotional problems. We aim to determine the levels of diabetes-specific emotional problems in diabetic individuals with high versus low levels of depression in a sample of 539 outpatients with diabetes (202 Dutch, 185 Croatian and 152 English). Subjects completed the Center for Epidemiological Studies Depression and the Problem Areas in Diabetes scales. Percentages of patients with high depression scores were: 39 and 34% (Croatian men and women), 19 and 21% (Dutch men and women), 19 and 39% (English men and women). Moreover, 79% (Croatian), 47% (Dutch) and 41% (English) of the patients with a severe depression score reported to have four or more serious diabetes-specific emotional problems. For patients with low depression scores, these percentages were: 29% (Croatian), 11% (Dutch) and 1% (English). Serious diabetes-specific emotional problems are particularly prevalent in depressed diabetes patients. Randomized controlled trials are warranted to test whether coverage of diabetes-specific issues during psychotherapy can further improve the treatment of depression in diabetes. 相似文献
6.
Lee YF John M Falconer A Edwards S Clark J Flohr P Roe T Wang R Shipley J Grimer RJ Mangham DC Thomas JM Fisher C Judson I Cooper CS 《Cancer research》2004,64(20):7201-7204
Metastasis is a major factor associated with poor prognosis in cancer, but little is known of its molecular mechanisms. Although the clinical behavior of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we have chosen leiomyosarcoma as a model for examining the relationship between gene expression profile and the development of metastasis in soft tissue sarcomas. Using cDNA microarray, we have identified a gene expression signature associated with metastasis in sarcoma that allowed prediction of the future development of metastases of primary tumors (Kaplan-Meier analysis P = 0.001). Our finding may aid the tailoring of therapy for individual sarcoma patients, where the aggressiveness of treatment is affected by the predicted outcome of disease. 相似文献
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Sarah Picaud Christopher Wells Ildiko Felletar Deborah Brotherton Sarah Martin Pavel Savitsky Beatriz Diez-Dacal Martin Philpott Chas Bountra Hannah Lingard Oleg Fedorov Susanne Müller Paul E. Brennan Stefan Knapp Panagis Filippakopoulos 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(49):19754-19759
10.
Chitra A. Shintre Ashley C. W. Pike Qiuhong Li Jung-In Kim Alastair J. Barr Solenne Goubin Leela Shrestha Jing Yang Georgina Berridge Jonathan Ross Phillip J. Stansfeld Mark S. P. Sansom Aled M. Edwards Chas Bountra Brian D. Marsden Frank von Delft Alex N. Bullock Opher Gileadi Nicola A. Burgess-Brown Elisabeth P. Carpenter 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(24):9710-9715
ABCB10 is one of the three ATP-binding cassette (ABC) transporters found in the inner membrane of mitochondria. In mammals ABCB10 is essential for erythropoiesis, and for protection of mitochondria against oxidative stress. ABCB10 is therefore a potential therapeutic target for diseases in which increased mitochondrial reactive oxygen species production and oxidative stress play a major role. The crystal structure of apo-ABCB10 shows a classic exporter fold ABC transporter structure, in an open-inwards conformation, ready to bind the substrate or nucleotide from the inner mitochondrial matrix or membrane. Unexpectedly, however, ABCB10 adopts an open-inwards conformation when complexed with nonhydrolysable ATP analogs, in contrast to other transporter structures which adopt an open-outwards conformation in complex with ATP. The three complexes of ABCB10/ATP analogs reported here showed varying degrees of opening of the transport substrate binding site, indicating that in this conformation there is some flexibility between the two halves of the protein. These structures suggest that the observed plasticity, together with a portal between two helices in the transmembrane region of ABCB10, assist transport substrate entry into the substrate binding cavity. These structures indicate that ABC transporters may exist in an open-inwards conformation when nucleotide is bound. We discuss ways in which this observation can be aligned with the current views on mechanisms of ABC transporters. 相似文献